Over the last two decades, stimuli-responsive “smart” hydrogels, which can respond reversibly to external stimuli, such as pH, temperature and electric field, have attracted a great deal of interest due to their potential applications in various fields especially in controlled drug delivery (Qiu and Park, Adv Drug Delivery Rev 53(3):321-339, 2001). In the recent years, a significant body of research has focused on the development of biocompatible magnetically-responsive nanoparticles for various drug delivery and biomedical applications, such as magnetic drug targeting, enzyme immobilization, hyperthermia anti-cancer treatment, and the magnetic resonance imaging for clinical diagnosis (Morales et al., Mater Sci Eng C 28:253-257, 2008; Kim et al., J Magnetism Magnetic Mater 225:256-261, 2001; Reynolds et al., J Am Chem Soc 122:8940-8945, 2000; Lübbe et al., Cancer Res 56:4686-4693, 1996; Bergemann et al., J Magnetism Magnetic Mater 194:45-52, 1999; Chan et al., J Magnetism Magnetic Mater 122:374-378, 1993; Jordan et al., J Magnetism Magnetic Mater 194:185-196, 1999; Dyal et al., J Am Chem Soc 125:1684, 2003). The efficiency of magnetic nanoparticles in most of these applications depends particularly on the particle size distribution and the morphology of the polymer/magnetic nanoparticles (Weissleder et al., Radiology 175:489-493, 1990; Thode et al., J Drug Targeting 5:35-43, 1997).
Magnetically-responsive hydrogel nanoparticles with high saturation magnetization and high susceptibility have the ability to trigger drug release upon applying external magnetic stimuli (Liva et al., J Magnetism Magnetic Mater 304, 397-399, 2006). The major advantage of this drug delivery technology is attributed to the magnetic characteristics of the carrier system, which can be controlled remotely, and the biocompatibility of both the encapsulated iron oxides nanoparticles (e.g., magnetite (Fe3O4) and maghemite (γ-Fe2O3)), and the polymeric hydrogel matrices. Superparamagnetic iron oxide nanoparticles (SPIONs), which can be easily magnetized and concentrated in a specific site by applying an external magnetic field and re-dispersed again once the magnetic field is removed, have received considerable interest for drug delivery purposes (McGill et al., IEEE Transaction on Nanobioscience 8(1):33-42, 2009).
Production of hydrogel nanoparticles typically utilizes toxic or bio-incompatible solvents. Moreover, the processing can be costly and particle size distributions are typically very broad. Thus, there is a need for new processes that can efficiently produce nanoparticles, and even larger microparticles, with desirable particle size distributions. There is also a need for new biocompatible polymeric systems that allow the production of hydrogel particles with optimal characteristics and that use biocompatible solvents relevant to actual clinical use. The methods and compositions disclosed herein address these and other needs.